DESCRIPTION Increasing evidence suggests that the nucleoside adenosine plays important roles in the regulation of adipocyte metabolism. Acting via A1 adenosine receptors (A1AR) adenosine decreases lipolysis and increases glucose uptake in adipocytes. Recent evidence suggests that there is increased adipocyte sensitivity to adenosine in leptin deficient or resistant states raising the possibility that leptin modulates adenosine action. Since A1AR activation can influence cellular cAMP stores, and changes in intracellular cAMP alter leptin secretion, it is also possible that adenosine regulates leptin release. It is, therefore, hypothesized that leptin and adenosine interact to potently influence adipocyte metabolism. To test this proposal, in vitro cultures of murine fat cells will be studied to examine adenosine and leptin interactions. It is anticipated that these studies will provide novel insights into humoral regulation of fat cell metabolism.